Efficient Solid‐Phase Synthesis of pppRNA by Using Product‐Specific Labeling1. Issue 18 (25th March 2014)

• Record Type: Journal Article
• Authors: Goldeck, M.; Tuschl, T.; Hartmann, G.; Ludwig, J.
• Is Part Of: Angewandte Chemie international edition. Volume 53:Issue 18(2014)
• Page Start: 4694
• Page End: 4698
• Publication Date: 2014-03-25
• Subjects: immunology -- medicinal chemistry -- oligonucleotides -- phosphorylation -- RNA; Chemistry -- Periodicals; 540
• DOI: 10.1002/anie.201400672
• Languages: English
• ISSNs: 1433-7851

Abstract

Abstract: A novel solid‐phase synthesis and purification strategy for 5′‐triphosphate oligonucleotides by using lipophilic tagging of the triphosphate moiety is reported. This is based on triphosphate synthesis with 5′‐O‐cyclotriphosphate intermediates, whereby a lipophilic tag, such as decylamine, is introduced during the ring‐opening reaction to give a linear gamma‐phosphate‐tagged species. This method enables the highly efficient synthesis of 5′‐triphosphorylated RNA derivatives and their gamma‐phosphate‐substituted analogues and will especially facilitate the advancement of therapeutic approaches that make use of 5′‐triphosphate oligonucleotides as potent activators of the cytosolic immune sensor RIG‐I. Abstract : Simple and straightforward : A strategy for the solid‐phase synthesis and purification of 5′‐triphosphate oligonucleotides through lipophilic tagging of the triphosphate moiety is reported. This method enables the efficient synthesis of 5′‐triphosphorylated RNA derivatives and their gamma‐phosphate‐substituted analogues and will facilitate the advancement of therapeutic approaches that make use of 5′‐triphosphate oligonucleotides as activators of the immune sensor RIG‐I.